Objective To describe patterns in maternal gestational weight gain (GWG) in healthy pregnancies with good maternal and perinatal outcomes.

Design Prospective longitudinal observational study.

Setting Eight geographically diverse urban regions in Brazil, China, India, Italy, Kenya, Oman, United Kingdom, and United States, April 2009 to March 2014.

Participants Healthy, well nourished, and educated women enrolled in the Fetal Growth Longitudinal Study component of the INTERGROWTH-21st Project, who had a body mass index (BMI) of 18.50-24.99 in the first trimester of pregnancy.

Main outcome measures Maternal weight measured with standardised methods and identical equipment every five weeks (plus/minus one week) from the first antenatal visit (<14 weeks’ gestation) to delivery. After confirmation that data from the study sites could be pooled, a multilevel, linear regression analysis accounting for repeated measures, adjusted for gestational age, was applied to produce the GWG values.

Results 13 108 pregnant women at <14 weeks’ gestation were screened, and 4607 met the eligibility criteria, provided consent, and were enrolled. The variance within sites (59.6%) was six times higher than the variance between sites (9.6%). The mean GWGs were 1.64 kg, 2.86 kg, 2.86 kg, 2.59 kg, and 2.56 kg for the gestational age windows 14-18+6 weeks, 19-23+6 weeks, 24-28+6 weeks, 29-33+6 weeks, and 34-40+0 weeks, respectively. Total mean weight gain at 40 weeks’ gestation was 13.7 (SD 4.5) kg for 3097 eligible women with a normal BMI in the first trimester. Of all the weight measurements, 71.7% (10 639/14 846) and 94.9% (14 085/14 846) fell within the expected 1 SD and 2 SD thresholds, respectively. Data were used to determine fitted 3rd, 10th, 25th, 50th, 75th, 90th, and 97th smoothed GWG centiles by exact week of gestation, with equations for the mean and standard deviation to calculate any desired centiles according to gestational age in exact weeks.

Conclusions Weight gain in pregnancy is similar across the eight populations studied. Therefore, the standards generated in this study of healthy, well nourished women may be used to guide recommendations on optimal gestational weight gain worldwide.

Objective To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Design Retrospective epidemiological analysis of data from the ACCORD trial.

Setting Diabetes clinics, research clinics, and primary care clinics.

Participants Patients were eligible for the ACCORD study if they had type 2 diabetes, a glycated haemoglobin (haemoglobin A1C) concentration of 7.5% or more during screening, and were aged 40-79 years with established cardiovascular disease or 55-79 years with evidence of subclinical disease or two additional cardiovascular risk factors.

Outcome measures Symptomatic, severe hypoglycaemia, manifest as either blood glucose concentration of less than 2.8 mmol/l (<50 mg/dl) or symptoms that resolved with treatment and that required either the assistance of another person or medical assistance, and all cause and cause specific mortality, including a specific assessment for involvement of hypoglycaemia.

Results 10 194 of the 10 251 participants enrolled in the ACCORD study who had at least one assessment for hypoglycaemia during regular follow-up for vital status were included in this analysis. Unadjusted annual mortality among patients in the intensive glucose control arm was 2.8% in those who had one or more episodes of hypoglycaemia requiring any assistance compared with 1.2% for those with no episodes (53 deaths per 1924 person years and 201 deaths per 16 315 person years, respectively; adjusted hazard ratio (HR) 1.41, 95% CI 1.03 to 1.93). A similar pattern was seen among participants in the standard glucose control arm (3.7% (21 deaths per 564 person years) v 1.0% (176 deaths per 17 297 person years); adjusted HR 2.30, 95% CI 1.46 to 3.65). On the other hand, among participants with at least one hypoglycaemic episode requiring any assistance, a non-significantly lower risk of death was seen in those in the intensive arm compared with those in the standard arm (adjusted HR 0.74, 95% 0.46 to 1.23). A significantly lower risk was observed in the intensive arm compared with the standard arm in participants who had experienced at least one hypoglycaemic episode requiring medical assistance (adjusted HR 0.55, 95% CI 0.31 to 0.99). Of the 451 deaths that occurred in ACCORD up to the time when the intensive treatment arm was closed, one death was adjudicated as definitely related to hypoglycaemia.

Conclusion Symptomatic, severe hypoglycaemia was associated with an increased risk of death within each study arm. However, among participants who experienced at least one episode of hypoglycaemia, the risk of death was lower in such participants in the intensive arm than in the standard arm. Symptomatic, severe hypoglycaemia does not appear to account for the difference in mortality between the two study arms up to the time when the ACCORD intensive glycaemia arm was discontinued.

Objectives To investigate potential determinants of severe hypoglycaemia, including baseline characteristics, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin (haemoglobin A1C) achieved during therapy.

Participants 10 209 of the 10 251 participants enrolled in the ACCORD study with type 2 diabetes, a haemoglobin A1C concentration of 7.5% or more during screening, and aged 40-79 years with established cardiovascular disease or 55-79 years with evidence of significant atherosclerosis, albuminuria, left ventricular hypertrophy, or two or more additional risk factors for cardiovascular disease (dyslipidaemia, hypertension, current smoker, or obese).

Main outcome measures Severe hypoglycaemia was defined as episodes of “low blood glucose” requiring the assistance of another person and documentation of either a plasma glucose less than 2.8 mmol/l (<50 mg/dl) or symptoms that promptly resolved with oral carbohydrate, intravenous glucose, or glucagon.

Results The annual incidence of hypoglycaemia was 3.14% in the intensive treatment group and 1.03% in the standard glycaemia group. We found significantly increased risks for hypoglycaemia among women (P=0.0300), African-Americans (P<0.0001 compared with non-Hispanic whites), those with less than a high school education (P<0.0500 compared with college graduates), aged participants (P<0.0001 per 1 year increase), and those who used insulin at trial entry (P<0.0001). For every 1% unit decline in the haemoglobin A1C concentration from baseline to 4 month visit, there was a 28% (95% CI 19% to 37%) and 14% (4% to 23%) reduced risk of hypoglycaemia requiring medical assistance in the standard and intensive groups, respectively. In both treatment groups, the risk of hypoglycaemia requiring medical assistance increased with each 1% unit increment in the average updated haemoglobin A1C concentration (standard arm: hazard ratio 1.76, 95% CI 1.50 to 2.06; intensive arm: hazard ratio 1.15, 95% CI 1.02 to 1.21).

Conclusions A greater drop in haemoglobin A1C concentration from baseline to the 4 month visit was not associated with an increased risk for hypoglycaemia. Patients with poorer glycaemic control had a greater risk of hypoglycaemia, irrespective of treatment group. Identification of baseline subgroups with increased risk for severe hypoglycaemia can provide guidance to clinicians attempting to modify patient therapy on the basis of individual risk.

Review methods All included studies were randomised controlled trials in children (including adolescents) or adults with type 1 diabetes that evaluated the effect of a psychological therapy (counselling, cognitive behaviour therapy, family systems therapy, and psychodynamic therapy) on control of diabetes. Data were extracted on sample size, age, duration of diabetes, type of psychological therapy, its mode of delivery, and type of intervention in control group.

Main outcome measures Glycaemic control measured by percentage of glycated haemoglobin and psychological distress. Pooled standardised effect sizes were calculated.

Results 29 trials were eligible for the systematic review and 21 trials for the meta-analysis. In the 10 studies of children and adolescents included in the meta-analysis, the mean percentage of glycated haemoglobin was significantly reduced in those who had received a psychological intervention compared with those in the control group (pooled standardised mean difference -0.35 (95% confidence interval -0.66 to -0.04), equivalent to a 0.48% (0.05% to 0.91%) absolute reduction in glycated haemoglobin. In the 11 studies in adults the pooled standardised mean difference was -0.17 (-0.45 to 0.10), equivalent to 0.22% (-0.13% to 0.56%) absolute reduction in glycated haemoglobin. Psychological distress was significantly lower in the intervention groups in children and adolescents (pooled standardised effect size -0.46, -0.83 to -0.10) but not in adults (-0.25, -0.51 to 0.01).

Conclusion Psychological treatments can slightly improve glycaemic control in children and adolescents with diabetes but have no effect in adults.

To examine the prevalence of psychiatric disorders in veterans of the Gulf war with or without unexplained physical disability (a proxy measure of ill health) and in similarly disabled veterans who had not been deployed to the Gulf war (non-Gulf veterans).

Design

Two phase cohort study.

Setting

Current and ex-service UK military personnel.

Participants

Phase 1 consisted of three randomly selected samples of Gulf veterans, veterans of the 1992-7 Bosnia peacekeeping mission, and UK military personnel not deployed to the Gulf war (Era veterans) who had completed a postal health questionnaire. Phase 2 consisted of randomly selected subsamples from phase 1 of Gulf veterans who reported physical disability (n=111) or who did not report disability (n=98) and of Bosnia (n=54) and Era (n=79) veterans who reported physical disability.

Main outcome measure

Psychiatric disorders assessed by the schedule for clinical assessment in neuropsychiatry and classified by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition.

Results

Only 24% (n=27) of the disabled Gulf veterans had a formal psychiatric disorder (depression, anxiety, or alcohol related disorder). The prevalence of psychiatric disorders in non-disabled Gulf veterans was 12%. Disability and psychiatric disorders were weakly associated in the Gulf group when confounding was adjusted for (adjusted odds ratio 2.4, 99% confidence interval 0.8 to 7.2, P=0.04). The prevalence of psychiatric disorders was similar in disabled non-Gulf veterans and disabled Gulf veterans ( 19% v 24%; 1.3, 0.5 to 3.4). All groups had rates for post-traumatic stress disorder of between 1% and 3%.

Conclusions

Most disabled Gulf veterans do not have a formal psychiatric disorder. Post-traumatic stress disorder is not higher in Gulf veterans than in other veterans. Psychiatric disorders do not fully explain self reported ill health in Gulf veterans; alternative explanations for persistent ill health in Gulf veterans are needed.

What is already known on this topicGulf veterans report medically unexplained symptoms more often than non-Gulf veteransThe clinical characteristics of ill health in Gulf veterans are not well known, and factors associated with ill health in Gulf veterans are poorly understoodWhat this study addsMost ill Gulf veterans do not have a formal psychiatric disorderThe rates for post-traumatic stress disorder are lowPsychiatric morbidity is not strongly associated with ill health in Gulf veteransThe rates for somatoform disorders are three times greater in disabled Gulf veterans than they are in disabled non-Gulf veterans

To determine how many veterans in a random sample of British veterans who served in the Gulf war believe they have “Gulf war syndrome,” to examine factors associated with the presence of this belief, and to compare the health status of those who believe they have Gulf war syndrome with those who do not.

Design

Questionnaire study asking British Gulf war veterans whether they believe they have Gulf war syndrome and about symptoms, fatigue, psychological distress, post-traumatic stress, physical functioning, and their perception of health.

Participants

2961 respondents to questionnaires sent out to a random sample of 4250 Gulf war veterans (69.7%).

Main outcome measure

The proportion of veterans who believe they have Gulf war syndrome.

Results

Overall, 17.3% (95% confidence interval 15.9 to 18.7) of the respondents believed they had Gulf war syndrome. The belief was associated with the veteran having poor health, not serving in the army when responding to the questionnaire, and having received a high number of vaccinations before deployment to the Gulf. The strongest association was knowing another person who also thought they had Gulf war syndrome.

Conclusions

Substantial numbers of British Gulf war veterans believe they have Gulf war syndrome, which is associated with psychological distress, a high number of symptoms, and some reduction in activity levels. A combination of biological, psychological, and sociological factors are associated with the belief, and these factors should be addressed in clinical practice.

What is already known on this topicThe term Gulf war syndrome has been used to describe illnesses and symptoms experienced by veterans of the 1991 Gulf warConcerns exist over the validity of Gulf war syndrome as a unique entityWhat this study adds17% of Gulf war veterans believe they have Gulf war syndromeHolding the belief is associated with worse health outcomesKnowing someone else who believes they have Gulf war syndrome and receiving more vaccinations were associated with holding the belief

To explore the relation between ill health after the Gulf war and vaccines received before or during the conflict. To test the hypothesis that such ill health is limited to military personnel who received multiple vaccines during deployment and that pesticide use modifies any effect.

Design

Cross sectional study of Gulf war veterans followed for six to eight years after deployment.

Setting

UK armed forces.

Participants

Military personnel who served in the Gulf and who still had their vaccine records.

Main outcome measures

Multisymptom illness as classified by the Centers for Disease Control and Prevention; fatigue; psychological distress; post-traumatic stress reaction; health perception; and physical functioning.

Results

The response rate for the original survey was 70.4% (n=3284). Of these, 28% (923) had vaccine records. Receipt of multiple vaccines before deployment was associated with only one of the six health outcomes (post-traumatic stress reaction). By contrast five of the six outcomes (all but post-traumatic stress reaction) were associated with multiple vaccines received during deployment. The strongest association was for the multisymptom illness (odds ratio 5.0; 95% confidence interval 2.5 to 9.8).

Conclusion

Among veterans of the Gulf war there is a specific relation between multiple vaccinations given during deployment and later ill health. Multiple vaccinations in themselves do not seem to be harmful but combined with the “stress” of deployment they may be associated with adverse health outcomes. These results imply that every effort should be made to maintain routine vaccines during peacetime.

To assess the variability among histopathologists in diagnosing and grading cervical intraepithelial neoplasia eight experienced histopathologists based at different hospitals examined the same set of 100 consecutive colposcopic cervical biopsy specimens and assigned them into one of six diagnostic categories. These were normal squamous epithelium, non-neoplastic squamous proliferations, cervical intraepithelial neoplasia grades I, II, and III, and other. The histopathologists were given currently accepted criteria for diagnosing and grading cervical intraepithelial neoplasia and asked to mark their degree of confidence about their decision on a visual linear analogue scale provided. The degree of agreement between the histopathologists was characterised by kappa statistics, which showed an overall poor agreement (unweighted kappa 0.358). Agreement between observers was excellent for invasive lesions, moderately good for cervical intraepithelial neoplasia grade III, and poor for cervical intraepithelial neoplasia grades I and II (unweighted kappa 0.832, 0.496, 0.172, and 0.175, respectively); the kappa value for all grades of cervical intraepithelial neoplasia taken together was 0.660. The most important source of disagreement lay in the distinction of reactive squamous proliferations from cervical intraepithelial neoplasia grade I. The histopathologists were confident in diagnosing cervical intraepithelial neoplasia grade III and invasive carcinoma (other) but not as confident in diagnosing cervical intraepithelial neoplasia grades I and II and glandular atypia (other). Experienced histopathologists show considerable interobserver variability in grading cervical intraepithelial neoplasia and more importantly in distinguishing between reactive squamous proliferations and cervical intraepithelial neoplasia grade I. It is suggested that the three grade division of cervical intraepithelial neoplasia should be abandoned and a borderline category introduced that entails follow up without treatment.

Objectives To examine the experiences of men after treatment for colorectal cancer, identify barriers to accessing services, and suggest improvements to providing information in primary and secondary care.

Results Most men treated for colorectal cancer experience erectile dysfunction as a consequence. Not all, however, want the same response from health professionals. Although, erectile dysfunction is profoundly stressful for most men, affecting self image, behaviour, and relationships, some do not regard it as a health priority. Many of the men were uninformed about erectile dysfunction and were unprepared for it, and the majority neither helped themselves nor asked for help. Almost none were receiving adequate, effective, and affordable care. Evidence of ageism was strong.

Conclusions Unlike patients with prostate cancer, men with colorectal cancer are not routinely offered information and treatment for erectile dysfunction. Greater coordination of care and consistent strategies are needed to tackle the unmet needs of this widely diverse patient group. Currently, clinicians are inadvertently neglecting, misleading, and offending such patients; better training could improve this situation, as might the reorganisation of services. Further research is needed to determine whether trained clinical nurse specialists in colorectal cancer units could coordinate ongoing care.

Objective To assess the accuracy of malaria diagnosis and treatment at primary level clinics in Afghanistan.

Design Prospective observational study.

Setting 22 clinics in two Afghan provinces, one in the north (adjoining Tajikistan) and one in the east (adjoining Pakistan); areas with seasonal transmission of Plasmodium vivax and Plasmodium falciparum.

Interventions Established (>5 years) microscopy (12 clinics in east Afghanistan), newly established microscopy (five clinics in north Afghanistan), and no laboratory (five clinics in north Afghanistan). All clinics used the national malaria treatment guidelines.

Main outcome measures Proportion of patients positive and negative for malaria who received a malaria drug; sensitivity and specificity of clinic based diagnosis; prescriber’s response to the result of the clinic slide; and proportion of patients positive and negative for malaria who were prescribed antibiotics. Outcomes were measured against a double read reference blood slide.

Results In health centres using clinical diagnosis, although 413 of 414 patients were negative by the reference slide, 412 (99%) received a malaria drug and 47 (11%) received an antibiotic. In clinics using new microscopy, 37% (75/202) of patients who were negative by the reference slide received a malaria drug and 60% (103/202) received an antibiotic. In clinics using established microscopy, 50.8% (645/1269) of patients who were negative by the reference slide received a malaria drug and 27.0% (342/1269) received an antibiotic. Among the patients who tested positive for malaria, 94% (443/472) correctly received a malaria drug but only 1 of 6 cases of falciparum malaria was detected and appropriately treated. The specificity of established and new microscopy was 72.9% and 79.9%, respectively. In response to negative clinic slide results, malaria drugs were prescribed to 270/905 (28.8%) and 32/154 (21%) and antibiotics to 347/930 (37.3%) and 99/154 (64%) patients in established and new microscopy arms, respectively. Nurses were less likely to misprescribe than doctors.

Conclusions Despite a much lower incidence of malaria in Afghanistan than in Africa, fever was substantially misdiagnosed as malaria in this south Asian setting. Inaccuracy was attributable to false positive laboratory diagnoses of malaria and the clinicians’ disregard of negative slide results. Rare but potentially fatal cases of falciparum malaria were not detected, emphasising the potential role of rapid diagnostic tests. Microscopy increased the proportion of patients treated with antibiotics producing a trade-off between overtreatment with malaria drugs and probable overtreatment with antibiotics.

Results Of 2756 patients with available data and included in the final analysis, 1871 (68%) did not receive postoperative NSAID treatment (controls) and 885 (32%) did. In the NSAID group, 655 (74%) patients received ibuprofen and 226 (26%) received diclofenac. Anastomotic leakage verified at reoperation was significantly increased among patients receiving diclofenac and ibuprofen treatment, compared with controls (12.8% and 8.2% v 5.1%; P<0.001). After unadjusted analyses and when compared with controls, more patients had anastomotic leakage after treatment with diclofenac (7.8% (95% confidence interval 3.9% to 12.8%)) and ibuprofen (3.2% (1.0% to 5.7%)). But after multivariate logistic regression analysis, only diclofenac treatment was a risk factor for leakage (odds ratio 7.2 (95% confidence interval 3.8 to 13.4), P<0.001; ibuprofen 1.5 (0.8 to 2.9), P=0.18). Other risk factors for anastomotic leakage were male sex, rectal (v colonic) anastomosis, and blood transfusion. 30 day mortality was comparable in the three groups (diclofenac 1.8% v ibuprofen 4.1% v controls 3.2%; P=0.20).

Conclusions Diclofenac treatment could result in an increased proportion of patients with anastomotic leakage after colorectal surgery. Cyclo-oxygenase-2 selective NSAIDs should be used with caution after colorectal resections with primary anastomosis. Large scale, randomised controlled trials are urgently needed.

Objective To assess the impact of rapid diagnostic tests on the diagnostic accuracy and treatment of malaria and non-severe fever in an Asian setting.

Design Patient randomised trial in primary level clinics.

Setting Two areas of Afghanistan where Plasmodium vivax and Plasmodium falciparum are endemic; one area with moderate transmission (eastern region) and one with low transmission (northern region).

Participants 5794 patients of all ages with suspected malaria enrolled by 80 clinicians in 22 clinics.

Interventions Malaria rapid diagnostic tests were compared with clinical diagnosis where no parasite diagnostic test was available, longer established field microscopy, and recently introduced microscopy.

Main outcome measures Proportion of patients appropriately treated with an antimalarial, defined as patients with P vivax who received chloroquine, patients with P falciparum who received artemisinin based combination therapy, and patients with no malaria parasites who did not receive an antimalarial. Secondary outcomes included diagnostic test accuracy and the proportion of patients negative for malaria who received antibiotics and antimalarials.

Conclusions In South and central Asian regions of low to moderate malaria transmission where clinics lack capacity for diagnosis with rapid diagnostic tests or microscopy, the introduction of the tests should be considered to improve clinical care, reduce the overuse of antimalarials, and improve disease surveillance.